The release of melanophore stimulating hormone (MSH) from the pars intermedia of the vertebrate pituitary is under an inhibitory control by an MSH release-inhibiting factor (MRIF) of hypothalamic origin. Studies are underway to determine the nature and mechanism of action of the proposed MRIF. Various neurohypophysical hormones and related substructures (the ring structures of neurohypophysical hormones) as well as neurotransmitters catecholamines, acetylcholine, serotonin) are being studied for their effects on MSH release. Pharmacological antagonists are being used to determine the receptor mechanisms by which biogenic amines and cholinergic agents mediate their inhibitory or stimulatory effects on MSH release. The ionic and metabolic requirements for MSH secretion are being determined as are the possible roles of microfilaments and/or microtubules for hormone secretion. The relationship of cyclic AMP levels of the pars intermedia to MSH release inhibition or stimulation is presently being assessed. Continued efforts toward determining the optional incubation conditions for the study of MSH-release mechanisms is underway.